A Study to investigate the Safety and Efficacy of ABT-494 Given with Methotrexate (MTX) in Subjects with Moderately to Severely Active Rheumatoid Arthritis (RA) Who Have Failed Anti-TNF Biologic Therapy

INTERVENTION: Product Name: ABT 494 3mg Pharmaceutical Form: Capsule INN or Proposed INN: ABT 494 Current Sponsor code: ABT 494 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 3‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use Product Name: ABT 494 12mg Pharmaceutical Form: Capsule INN or Proposed INN: ABT 494 Current Sponsor code: ABT‐494 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 12‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use CONDITION: Moderately to Severely Active Rheumatoid Arthritis (RA) ; MedDRA version: 17.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: The primary objective is to compare the safety and efficacy of multiple doses of ABT‐494 versus placebo in moderately to severely active RA subjects on stable background MTX therapy with inadequate response or intolerance to anti‐TNF biologic therapy. Primary end point(s): ACR20 response rate. Secondary Objective: Not applicable Timepoint(s) of evaluation of this end point: Week 12 SECONDARY OUTCOME: Secondary end point(s): ACR50/70 response rates, the proportion of subjects achieving low disease activity (LDA) (2.6 = DAS28 [CRP] < 3.2) or clinical remission (CR) (DAS28 [CRP] < 2.6), and the proportion of subjects achieving CR (DAS28 [CRP] < 2.6) Timepoint(s) of evaluation of this end point: Week 12 INCLUSION CRITERIA: 1. Adult male or female, at least 18 years old. 2. Diagnosed with RA based on either the 1987‐revised American College of Rheumatology (ACR) classification criteria or the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria for = 3 months. 3. Subjects have been treated with 1 or more anti‐TNF biologics (no maximum cap) for = 3 months but continue to exhibit active RA, or had to discontinue due to intolerability or toxicity. In addition, subjects with prior exposure to non‐anti TNF biologic(s) (no maximum cap) (e.g., abatacept, rituximab, anakinra, or tocilizumab) are allowed. 4. Have active RA as defined by the following minimum disease activity criteria: • = 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits. • = 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits. • hsCRP > Upper Limit of Normal (ULN) OR positive for both rheumatoid factor (RF) a